Understanding the factors that cause people to transition from normal aging to preclinical Alzheimer's disease (AD) to mild cognitive impairment, and subsequently convert to dementia is the central focus of the University of California Alzheimer's Disease Research Center (UCI ADRC). The UCI ADRC integrates basic and translational science and clinical domains to elucidate the heterogeneity in the clinical sub-types of AD, including early-onset, genetic, and late-onset forms. As such, we follow three valuable cohorts: (1) longitudinal cohort, which includes older adults with preclinical and early-stage AD, (2) Down syndrome cohort, representing the largest genetically at-risk population for AD, which enables us to describe the role of amyloid deposition in the early years of the life span and the particular vulnerability that this might impart for developing AD, and (3) the oldest-old, as part of the 90+ Autopsy Study, which show great disparity between AD pathology and cognitive loss. The UCI ADRC brings energetic and innovative multi-dimensional and multi- disciplinary approaches toward solving this insidious disease and also contributes to several national efforts.